The purpose of the Blood Drawing for Component Preparation is to obtain cells, proteins, DNA and lipids from healthy volunteers and dyslipidemic subjects for use in research. Our laboratory is focused in trying to identify common mutations in the population that contribute to the variation in lipoprotein levels and atherosclerosis susceptibility between people. In this work, we use the lipoprotein transport genes as candidate genes, although we are also trying to identify other genes that might be important such as those which regulate cholesterol absorption or the blood vessel wall response to hypercholesterolemia. Recent work suggests that mutations which affect the level of expression of the apo CIII gene may cause hypertriglyceridemia and our lab is trying to determine how this occurs. Another area of research relates to studies of apolipoprotein gene expression and how this might influence plasma lipoprotein levels. Lipoproteins (VLDL, LDL, and HDL) are prepared from human subjects and used in experimentation involving the response of cultured cells to lipoproteins and studying lipoprotein modification and oxidation. These studies are relevant to atherosclerosis research, as we are studying cholesterol loading of cells and cholesterol efflux from cells, as well as leukocyte-endothelial cell interactions. In additional studies, DNA is prepared from human blood samples and used to look at human genetic variation and association with lipoprotein metabolism. One human genetic variation that we have studied is at the apoE locus, where there are three common alleles coding for three allelic isoforms, called E2, E3, and E4. The E4 allele is associated with increased LDL cholesterol, increased risk of coronary vascular disease, and most strikingly with Alzheimer's disease. We have begun to study the properties of E4 which may account for their association with human disease.